RNA cleaving DNA Thresholder Controlled by Concentrations of miRNA Cancer Marker

Authors: Gomes De Olivejra A.Z.Dubovichenko M.V., Ahmed E., Wanjohi J.M., Karamisheva S.P., Kolpashchikov D.M.


Oligonucleotide gene therapy (OGT) agents suppress specific mRNAs in cells and thus reduce expression of targeted genes. The ability to unambiguously distinguish cancer from healthy cells can solve the low selectivity problem of OGT agents. Cancer RNA markers are expressed in both healthy and cancer cells with higher expression level in cancer cells. Here we designed a DNA‐based construct, named DNA thresholder (DTh) that cleaves targeted RNA only at high concentrations of cancer marker RNA demonstrating delay at low marker concentrations. The RNA cleaving activity can be adjusted within one order of magnitude of the cancer marker RNA concentration by simple redesigning ThD. Importantly, DTh recognizes cancer marker RNA, while cleaving other targeted RNA, which offers a possibility to suppress vital genes exclusively in cancer cells thus triggering their death. DTh is a prototype of computation‐inspired molecular device for controlling gene expression and cancer treatment.

Read full: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cbic.202000769